Immunosuppressive Therapy and Immunomodulatory Agents Flashcards Preview

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Flashcards in Immunosuppressive Therapy and Immunomodulatory Agents Deck (25):
1

Long term immunosuppressive therapy

Susceptibility to bacterial infections (common)
- ex: cystitis, pyoderma, pneumonia
Overwhelming, unusual infections
- fungal, protozoal, parasitic

2

Mechanisms of immunosuppression

- decrease antibody synthesis by plasma cells (days)
- decrease antibody-cell binding affinity
- impair mononuclear phagocytic system cell destruction of antibody-coated cells (hours)

3

Common therapies

- glucocorticoids
- azathioprine
- cyclosporine

4

Additional medications

- mycophenolate
- vincristine
- chlorambucil
- leflunomide
- cyclophosphamide

5

Glucocorticoids

Prednisone, prednisolone, dexamethasone
- mainstay of immunosuppressive therapy

6

Every animal requires some small degree of _______

Glucocorticoids

7

Corticosteroid mechanisms

Once in the nucleus, binds to specific DNA sequences
- enchance/inhibit transcription of genes
- induce or inhibit protein translation

8

Corticosteroid effects

Effects on complement and rapid down-regulation of Fc receptor expression on macrophages leads to the reduction of phagocytosis of opsonized cells

9

Additional immunosuppressive effects

- decrease egress of cells from the blood
- suppress macrophages and neutrophil bactericidal functions
- inhibit amplification pathways of the complement cascade
- decrease antigen presentation to Th cells
- anti inflammatory properties

10

Glucocorticoid therapy: acute side effects

Polyuria/polydipsia
- increase urination and water consumption
Polyphagia
- increase food intake
Panting
+/- GI ulcerations

11

Glucocorticoid therapy: chronic side effects

- alopecia
- thin skin
- pot belly
- hepatomegaly
- muscle weakness

12

Local acting steroids

Local effect and fewer systemic side effects
- poor systemic absorption

13

Combination immunosuppressive therapy

Increase immunosuppression
- drugs of different mechanisms of action
- "dose sparing" effect with side effects

14

Immunosuppressive agents are ______ used in dogs

Commonly
- glucocorticoid side effects common
- immunosuppressive agents often well tolerated

15

Immunosuppressive agents are _____ used in cats

Rarely
- can tolerate chronic high doses of steroids
- immunosuppressive agents are poorly tolerated

16

Azathioprine

Interferes with purine synthesis
- does not directly reduce serum antibody production
- indirect reduction in lymphocyte proliferation
- can enter all cells, but only benefits rapidly dividing cells

17

Azathioprine side effects

- myelosuppression
- acute pancreatitis
- hepatopathy
- GI
Combo therapy with prednisone minimizes side-effects

18

What part of T cell activation directly correlates with B cell activation?

Th1 (IL-2, IFN-y) ---> plasma cells --> antibody secretion

19

Cyclosporine

Decreases antibody synthesis
- impairs IL-2
- reduces lymphocyte activation
= reduces T cell and then B cell proliferation

20

Cyclosporine side effect

- myelosuppression
- GI
- refractory cystitis or bladder neoplasia

21

Vincristine

Disrupts assembly of mitotic spindle in mitosis
- IMTP: increases platelet counts = impairs phagocytosis of opsonised platelets by impairing microtubule assembly in macrophages

22

Vincristine binds to ____ and targets_____

Platelets; macrophages

23

Management of immune-mediated blood disorders

High dose intravenous immunoglobulins

24

Human intravenous immunoglobulin

Competitively inhibits binding of canine IgG to monocytes by saturation of Fc receptors
- prevention of phagocytosis of antibody coated RBC and platelets

25

hIVIG

- minimal toxicity, but expensive
- may increase risk of blood clots
- availability is a major issue